Microtubule “Plus-End-Tracking Proteins” The End Is Just the Beginning

be a distinct class of accessory factors, which we term " plus-end-tracking proteins " or ϩTIPs. These MAPs are among the most conserved components of the MT cy-toskeleton. They localize to the MT plus end, and in living cells, they mark growing plus ends and thus give The Children's Hospital the appearance of " tracking. " Recently, studies from a Harvard Medical School variety of organisms have implicated ϩTIPs in the local 44 Binney Street control of MT assembly, and in the attachment of MTs Boston, Massachusetts 02115 to the cell membrane or kinetochore. CLIP-170 Family ϩTIPs Human CLIP-170 is the prototype ϩTIP (Perez et al., Microtubule (MT) polymers are the building materials for 1999 and references therein). The CLIP-170 family also many important shapes in the cell. A central puzzle includes the neural-specific paralog CLIP-115, fission about MTs is how they are so easily assembled into yeast tip1p, and budding yeast Bik1p (Akhmanova et different structures. A general answer has been at hand al., 2001 and references therein; Brunner and Nurse, for some time: the MT polymer is highly dynamic, and 2000 and references therein). What we refer to as plus-in the presence of the right accessory factors, MTs self-end tracking describes the appearance of green fluores-assemble into the desired forms. Thus, the accessory cent protein (GFP) tagged CLIP-170 as observed by factors—MT-associated proteins (MAPs) and MT-based video microscopy in living cells (Figures 1A and 1B). The motors—are thought to be the primary controls for the CLIP-170 signal is seen as a comet-like streak that skirts shape of MT structures in the cell. along the growing plus ends of MTs. The distinct MT Microtubules are hollow tubes composed of protofila-binding domain of CLIP-170, the CAP-Gly domain, is ments of ␣-and ␤-tubulin dimers organized in a head-necessary for plus-end tracking. Fluorescent speckle to-tail fashion. MTs are nucleated from their minus ends, analysis demonstrates that the CLIP-170 tracking be-located at microtubule organizing centers, in most cases havior is due to treadmilling of CLIP-170 molecules; the centrosome. Like the tentacles of an octopus, the CLIP-170 binds the polymerizing end of the MT and then plus ends explore the intracellular space through alter-falls off behind the region of growth (Figures 1A and 1B nating periods of growth and shrinkage, a behavior and legend; Perez et al., 1999; also see supplemental which is termed dynamic instability. Through a " search movies to Perez et …